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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal release of endothelium-derived relaxing factor (EDRF) and prostacyclin from intact vascular endothelium may inhibit continuously platelet aggregation. If local platelet aggregation occurs, platelet-derived adenine nucleotides stimulate the release of EDRF. Stimulated EDRF release may override the direct vasoconstrictor effects of other platelet products such as thromboxane and serotonin resulting in local vasodilatation. In addition, stimulation of EDRF release by adenine nucleotides may inhibit further platelet adhesion and aggregation by a feedback mechanism. Thus, intact vascular endothelium may play an important role in the defense against platelet deposition and vasospasm. In atherosclerosis, basal and stimulated release of EDRF is markedly reduced. Endothelial dysfunction will impair this protective mechanism and will favour vasoconstriction and further platelet disposition. Occurrence of occlusive thrombus formation in patients with coronary artery disease may be pathophysiologically related to this impairment of endothelial defense.
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PMID:Platelets, endothelium-dependent responses and atherosclerosis. 175 24

We have explored earlier evidence that premature atherosclerosis in homocystinuria is triggered by homocysteine-induced loss of vascular endothelium. We used a reproducible sluicing assay to test in vitro detachment of human arterial endothelial cells. Cell detachment was induced by exposure of cultured endothelial cells to the sulphydryl-containing amino acids homocysteine and cysteine, whereas methionine, alanine, valine and isoleucine at comparable concentrations were ineffective. This cellular detachment was greatly diminished by growth of the endothelial cells on fibronectin coated- rather than plain tissue culture dishes. Considerably higher concentrations of homocysteine were required for in vitro effects than are associated with atherogenesis in homocystinuria, and despite the cysteine associated changes, cysteine itself is not known to be related to atherogenesis. These data suggested that in vitro detachment of cultured endothelial cells, induced by sulphydryl-containing amino acids, may have marginal relevance to mechanisms of atherogenesis in homocystinuria.
Atherosclerosis 1991 Nov
PMID:Human arterial endothelial cell detachment in vitro: its promotion by homocysteine and cysteine. 181 56

Recently, platelet factor 4 (PF4) release by heparin (heparin-releasable PF4) has been examined as a useful marker of the interaction between the substances liberated from circulating platelets and the vascular endothelium. We compared the plasma levels of PF4 and beta-thromboglobulin (beta-TG) after intravenous heparin injection in patients with coronary artery disease (CAD) and normal control subjects. We also studied the effects of low-dose aspirin (81 mg/day) on the plasma level of heparin-releasable PF4 in the CAD patients. Blood samples were obtained before and 5 min after the intravenous injection of heparin (1,000 IU) from 23 patients with CAD and 15 normal control subjects. Although the plasma beta-TG level remained unchanged after heparin injection, the plasma PF4 level markedly increased in both groups. There was a significant difference in plasma PF4 levels at 5 min after heparin injection between the CAD group (100.1 +/- 38.1) and the control group (61.0 +/- 24.0) (p less than 0.01). The PF4/beta-TG ratio after heparin injection was also higher in the CAD group than in the control group (p less than 0.01). There was a correlation between the PF4/beta-TG ratio after heparin and the Gensini CAD score, which defines the severity of coronary atherosclerosis (r = 0.489, n = 23, p less than 0.01). Low-dose aspirin was administered to 11 CAD patients for 246.0 +/- 28.8 days. Blood samples for the assay of PF4 and beta-TG were obtained as stated above, and platelet aggregation, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels were also measured before and during aspirin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin-releasable platelet factor 4 in patients with coronary artery disease. 154 Oct 73

Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium-dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis.
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PMID:Endothelium-derived relaxing and contracting factors. 187 96

In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation.
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PMID:Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. 204 72

Prostacyclin and endothelium-derived relaxing factor (or nitric oxide) are unstable mediators produced by the vascular endothelium, that are important for local regulation of platelet behavior and blood flow. This review focuses on the basic biochemistry and pharmacology of prostacyclin, its interactions with nitric oxide and nitrovasodilator drugs, and the implications of disturbances in this system for vascular disease, particularly hypertension and atherosclerosis. Prostacyclin and its stable analogs are also finding limited therapeutic applications in preservation of platelet function, pulmonary hypertension, and investigation into the cytoprotective and antiatherosclerotic properties is continuing.
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PMID:Prostacyclin and vascular function: implications for hypertension and atherosclerosis. 208 4

This paper review the actual knowledges about the physiological role of nitric oxide, sintetized from amino acid L-arginine. The nitric oxide sintetized in the vascular endothelium has a fundamental role in vascular tone, blood flow and arterial pressure control, acting stimulating guanylate cyclase on vascular smooth muscle. Nitric oxide could be considered the endogenous nitrovasodilator. Its action on the cardiovascular system are imitated by nitroglycerine, sodium nitroprusside and related compounds. Probably the disturbance in the synthesis or release of nitric oxide may be involved in the pathophysiology of hypertension, vasospasm and atherosclerosis. Recently has been shown that nitric oxide synthesis from L-arginine also occurs in other different cells like macrophages, central nervous system, liver, neutrophils, adrenal glands, playing different biological effects. Changes in nitric oxide synthesis or action in those systems, could be related to different pathological disorders as inflammation, atherosclerosis and cancer. The found of a substance as simple as nitric oxide, let suppose that we are in the presence of a biological mediator with a very early evolutionary origin, probably widespread in all the animal kingdom, and which represents the universal transduction system for activation of the soluble guanylate cyclase enzyme.
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PMID:[Nitric oxide: from endogenous vasodilator to biologic mediator]. 209 54

Leaky endothelial junctions associated with cell turnover have been suggested to be a hydrophilic pathway for the transport of macromolecules across the vascular endothelium. To demonstrate focal increases in endothelial permeability, the occurrence of localized uptake of macromolecules in the rat thoracic aorta was studied at various time periods after intravascular administration of Evans blue-albumin (EBA) complexes. With fluorescence microscopy, EBA uptake in the rat thoracic aorta was visible either as discrete spots or as larger areas in both en face and cross-sectional preparations. The average size of EBA leaky spots increased with dye circulation time, indicating that there is a continuous influx of macromolecules through the transiently leaky junctions in these foci with subsequent diffusion in the vessel wall. There was heterogeneity in EBA spot size distribution, suggesting that endothelial cells undergoing turnover in different phases of the cell cycle might exhibit different extents of junctional leakage to macromolecules. The technique of [3H]thymidine labeling autoradiography was applied to en face preparations of the rat thoracic aorta for identifying replicating endothelial cells. The correlation of EBA leakage with [3H]thymidine-labeled endothelial cells was determined. Only 26% of endothelial cells with nuclear incorporation of [3H]thymidine were shown to be associated with EBA leaky foci. This lack of correlation suggests that alterations in endothelial junctional permeability accompanying cell turnover might occur only in some limited time periods of the cell cycle, e.g., the mitotic (M) phase, rather than the whole period of [3H]thymidine labeling.
Atherosclerosis 1990 Dec
PMID:Temporal and spatial changes in macromolecular uptake in rat thoracic aorta and relation to [3H]thymidine uptake. 210 86

We have investigated the effect of glucose on the release of endothelin-1-like immunoreactivity (ET-1-LI) from cultured bovine aortic endothelial cells. Elevation of glucose concentrations in cultured media from 5.5 to 11.1 or 22.2 mM significantly stimulated ET-1-LI release from cultured endothelial cells. An aldose reductase inhibitor did not affect the high glucose-induced ET-1-LI release. These findings suggest the possibility that hyperglycemia in diabetic patients enhances ET-1-LI release at the local site of vascular endothelium, which might be involved in the developments of vascular complications and atherosclerosis.
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PMID:Enhanced secretion of endothelin-1 by elevated glucose levels from cultured bovine aortic endothelial cells. 211 22

Atherosclerotic lesions are characterized by lipid infiltration in regions with high rates of endothelial cell turnover. The present investigation was designed to elucidate the route of macromolecular transport across vascular endothelium. The aorta and vena cava of male Sprague-Dawley rats were perfusion-fixed after the intravenous injection of Evans-blue albumin (EBA) or horseradish peroxidase (HRP). Fluorescence microscopic examination of en face preparation of the aorta stained with hematoxylin allowed the identification of endothelial cells that underwent mitosis, together with the localization and quantification of fluorescent spots for EBA leakage. The HRP specimens were subjected to histochemical treatment, and HRP leakage was seen as brown spots under the light microscope. Silver nitrate stain was added in both EBA and HRP studies to outline cell boundaries and to visualize stigmata, stomata, and dead cells. In the aorta, almost every dividing cell showed junctional leakage to albumin and HRP, with clustering of leaky spots around the branch orifices. Time-dependent studies showed gradual increases in the diameter and number of these heterogeneously sized leaky spots, which finally fused to sizes corresponding to the "blue areas" for EBA or "brown areas" for HRP. Compared with arteries, veins had fewer mitotic cells, but more dead cells and diffuse dye-staining areas, indicating a more rapid transport of macromolecules. The leaky spots in the artery were associated mainly with mitotic cells, dead cells, and stigmata, whereas those in the vein occurred primarily at regions with dead cells. These results suggest that the preferential association of the enhanced transport of macromolecules with mitosis in the arterial as compared to venous endothelium and the differential behavior in transmural transport between arteries and veins may form the basis for the predilection of atherosclerosis in arteries.
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PMID:Macromolecular transport across arterial and venous endothelium in rats. Studies with Evans blue-albumin and horseradish peroxidase. 218 Mar 95


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